Cellular endocrinology/paracrinology/autocrinology is the science of dissection and reconstitution of isolated cells and their environment in order to understand the physiology of the regulation of growth, function and differentiation. This knowledge applied to particular cell types that compose particular tissues is essential to understand and intervene in metabolic disease associated with specific tissues. This program seeks to understand the metabolic basis of. disease by application of these cellular level principles with modern protein chemical, molecular biological and genetic approaches The program is composed of four interrelated, but novel, projects which address specific questions concerning growth, function and differentiation of vascular, liver, adipose and thymic tissues. Two projects consider detailed molecular problems concerning the nature of the receptor, the proximal signal generated by factor (vascular endothelial cell growth factor and heparin-binding fibroblast growth factor)-receptor interaction and the control of the resulting signal. Two projects explore the integration of the EGF-receptor kinase interaction with the phospholipase A2/prostaglandin signal pathway in vitro and in vivo. The projects are backed by state-of-the-art protein chemistry and molecular core laboratories, the latter of which includes proposed establishment of a transgenic animal facility.